A wide variety of bacteria and bacterial fractions have been found to stimulate the resistance of experimental animals to challenge with immunologically unrelated syngeneic tumors. The actual mechanism of the phenomenon; non-specific stimulation of tumor resistance, is not understood. Recent advances on cellular immunity and cell cooperation in antibody synthesis have delineated a conceptual framework and techniques which enable us to pose specific questions about this complex phenomenon and elucidate its mechanism: Thus in the inductive phase, is specific host immunity to the organism or its fractions necessary for tumor resistance, or do the materials act as non-antigen-specific stimulators? In the effector phase, is tumor resistance the result of a non-specific cytotoxicity (or inhibition of cell growth), or is resistance due to an elevated (or newly induced) specific anti-tumor immunity? What cell or cells mediate these reactions, and is there cooperation between them? These questions will be explored using Listeria monocytogenes (LM) and methanol extraction residue (MER) of BCG, both of which have previously been shown to stimulate resistance to tumor challenge. Optimal conditions for demonstration of tumor resistance will be determined in several model tumor systems, and, by combining cells for tumor challenge with the specific bacterial antigen, the requirement for specific bacterial immunity will be assessed. Then we shall attempt to passively transfer tumor resistance with lymphoid cells from LM and MER treated mice and determine the requirement of sensitized cell populations for additional contact with bacterial antigen in non-specific resistance. The cellular basis of transferred resistance will be delineated with defined cell populations (Thymus-derived lymphocytes, bone marrow derived lymphocytes, macrophages, alone or in combination with each other or normal cells). This approach should tell us which host cells are necessary for non-specifically induced tumor resistance and characterize the antigenically specific and non-specific components. By monitoring the immune response in treated, challenged animals, we can determine if non-specific tumor resistance results in increased specific tumor immunity.